In the past 50 years or so, corticosteroids have been used in a broad spectrum of inflammatory conditions of the eye. In fact, corticosteroids belong to the class of therapeutics the most frequently prescribed in ophthalmology. In particular, topical corticosteroids have revolutionized the practice of ophthalmology and ophthalmic care when it comes to preventing or treating ocular inflammation due to trauma, chemical, infective, allergic or other causes. The most commonly used corticosteroids for topical ocular administration are prednisolone, fluorometholone, dexamethasone, rimexolone, and medrysone.
Corticosteroids are synthetic drugs that mimic steroid hormones naturally produced by the body. These steroid hormones have a wide variety of actions and control functions and are involved in a number of important physiological systems including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism and blood electrolyte levels. In addition to regulating inflammation, corticosteroids also have the ability to affect these other physiological systems, resulting in many potential risks and side effects.
As with most therapeutic drugs, the majority of side effects of corticosteroids are more pronounced with systemic therapy. However, they may occur with all routes of administration. For example, there are several potentially severe ocular side effects that can result from topical corticosteroid use. In particular, topical corticosteroid therapy can cause an increase in intra-ocular pressure (IOP). If IOP remains elevated for a length of time, glaucoma can occur with corresponding optic nerve damage and visual field loss. IOP elevation can generally be reversed by discontinuation of the treatment. Another potential side effect that can result from topical corticosteroid use is the development of posterior subcapsular cataracts, which can be visually debilitating and require surgical removal. Topical corticosteroid use can also lead to an increase in corneal thickness, mydriasis (an excessive dilation of the pupil) and ptosis (dropping of the upper eyelid).
Side effects of topical corticosteroid therapy are generally directly related to the dosage and duration of treatment and are more often observed with the use of potent corticosteroids, such as dexamethasone. These side effects are believed to result, at least in part, from penetration of the corticosteroid in internal ocular tissues, such as the aqueous humor. The effectiveness of topical corticosteroid therapy is thus severely limited by these unwanted effects since it is often administered for a shorter period of time than necessary, and/or utilizes a less potent agent than necessary.
Therefore, there is still a need in the art for improved approaches to eliminate or reduce side effects associated with topical administration of corticosteroids in the treatment of eye diseases or conditions.